10-76246379-A-G

Variant names:

• chr10-76246379-A-G
• rs1247487
• NM_001305581.2:c.517-78022A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.517-78022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,004 control chromosomes in the GnomAD database, including 22,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22430 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 1 publications found

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

LRMDA Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 7

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.517-78022A>G		intron	N/A	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.433-78022A>G		intron	N/A	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.871-78022A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.517-78022A>G		intron	N/A	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.433-78022A>G		intron	N/A	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.871-78022A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82218 AN: 151886 Hom.: 22415 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82255 AN: 152004 Hom.: 22430 Cov.: 32 AF XY: 0.542 AC XY: 40252 AN XY: 74290

African (AFR) AF: 0.479 AC: 19860 AN: 41454

American (AMR) AF: 0.570 AC: 8707 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1837 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2978 AN: 5144

South Asian (SAS) AF: 0.649 AC: 3125 AN: 4816

European-Finnish (FIN) AF: 0.483 AC: 5102 AN: 10560

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38611 AN: 67974

Other (OTH) AF: 0.573 AC: 1206 AN: 2106

Alfa AF: 0.543 Hom.: 3802

Bravo AF: 0.546

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.50
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1247487; hg19: chr10-78006137;